Controversial Avandia Study Faces FDA Scrutiny

A large Avandia study could be terminated by the U.S. Food & Drug Administration (FDA) over ethical concerns. The FDAâ€™s decision on whether to continue the trial, known as TIDE, could ultimately impact whether the controversial diabetes drug is allowed to remain on the market.

Avandia has been the subject of safety concerns for several years. In November 2007, a black box warning â€“ the FDA’s strongest safety warning â€“ detailing Avandiaâ€™s association with myocardial ischemia was added to the drugâ€™s labeling. The black box was added after the Cleveland Clinic published a meta- analysis of 42 clinical trails that showed patients taking Avandia had a 43-percent higher risk of having a heart attack. Earlier this year, the Senate Finance Committee released a report detailing its 2-year Avandia investigation. According to the report, in July 2007 the FDAâ€™s own scientists estimated that Avandia was responsible for more than 80,000 heart attacks.

Since the release of the Senate report, calls have increased for the FDA to pull Avandia off the market. The FDA is conducting another safety review of Avandia, the results of which will be discussed at a public meeting in July.

The TIDE trial is comparing Avandia with another diabetes drug called Actos. Actos has not raised as many safety concerns as Avandia, and according to the Journal, some scientists inside and outside the FDA have said it is unethical to compare a drug with known cardiac risks with a seemingly safer alternative.

In March, FDA Commissioner Margaret Hamburg wrote to Senator Charles Grassley (R-Iowa), one of the signatories of the senate Finance Committee report, telling him that the agency is reassessing the Avandia versus Actos trial “based on expert input and our own analysis.â€

Hamburg has also asked the Institute of Medicine, a government scientific panel, to review the ethics of such head-to-head studies like TIDE. In addition, Hamburg has asked a senior advisor to review the FDA’s decision-making on drug safety, including how much evidence the agency needs to pull a drug from the market.

Though neither of these reviews targets Avandia specifically, the Journal points out that both will be completed before the July advisory committee meeting on Avandia. It is likely that that their conclusions will be considered by the advisory panel.

As to Avandiaâ€™s future, Joshua Sharfstein, Hamburgâ€™s principle deputy, told The Wall Street Journal that whatever decision is made regarding TIDE, it “cannot be de-linked from the agency’s view of Avandia.â€ This, the Journal said, indicates that if the FDA halts TIDE, it could also ask Glaxo to halt sales of Avandia.